Phthalides



2,842,556 PatntedJulyB, .1958

PHTHALIDES Donald D. Wheeler, and David C. Young, Midland, Mich, assiguors, to The Dow Qhemicalfiompany, Midland,

ch-r awrp ati n Q tD aW No Drawing. Applicationduly 5,4956

a Serial Noa595g857 This invention is concerned with phthalides having the formula In this and succeeding formulae X represents oxygen or sulfur. The new compounds are light-colored solids somewhat soluble in organic solvents such as acetone and ethanol, and substantially insoluble in water. The compounds are useful insecticides. They also have antimicrobial properties and are adapted to be employed as toxic constituents in disinfectant preparations.

The above compounds may be prepared by causing phthalaldehydic acid to react with a biuret having the formula to produce the desired phthalide and water of reaction. The terms phthalaldehydic acid and 3-hydroxyphthalide refer to a compound having the structure OH ';H

Phthalaldehydic acid is often represented in the literature as having the structure CHO COOH

However, the acid employed in this invention and prepared as hereinafter described exists almost entirely in the 3-hydroxyphthalide ring structure, as indicated by a study of its infrared absorption spectrum. Infrared data also indicate the phthalide products to have the ring structure.

In the synthesis, good results are obtained when substantially equimolar proportions of each reactant are employed. The reaction takes place smoothly in the temperature range of from to 150 C. The reaction is preferably carried out in the presence of a solvent as reaction medium. Suitable solvents include water, benzene and 2-butanone. Generally, the product precipitates in the reaction mixture and may be recovered .by;-filtrati on. Alternatively, the solvent. may. be removed by-,vaporization .;and the product recovered as a residue.

In one method offlcarry ing, outathereaction, equimolai amounts of phthalaldehydic acid qand the appropriate biuretaremixed with or dissolved in. an-organicssolven1 suchas 2-butanone orbenzene. ,-The-resulting mixture is heated under reflux for frorn 0.5 to 4 hours. -Usually the phthalide, product precipitates during the ;heatingpe- ;.riod. After'completionof the hcating,.the mixture is cooled, and theproduct separated therefrombylfiltra .tion. If, desired, -the1 .latter may be purified by ,washing or recrystallization. I

In an alternative method of carrying out the reaction, phthalaldehydic acid is dissolved in a sufiicient amount of warm water and mixed with an aqueous solution containing an equiinolar amount of the appropriate biuret. A reaction takes place with the formation of the desired phthalide product which precipitates in the reaction mixture. The resulting mixture is warmed at 90 C. for 10 to minutes to complete the reaction. The mixture is then cooled and filtered to obtain the desired product. The product may be purified, if desired, as previously described.

The following examples illustrate the invention, but are not to be construed as limiting.

Example 1.-3-(3-carbamoylureido)phthalide KI .C/

24.2 grams (0.2 mole) of biuret monohydrate, 60.0 grams (0.4- mole) of phthalaldehydic acid and milliliters of water were mixed and heated on the steam bath for 3 hours. During the course of the heating a solid precipitated in the mixture. The mixture was then cooled in an ice bath to precipitate further product and then filtered to isolate a 3-(3-carbamoylureido)- phthalide product. The latter, after washing successively with water and alcohol and then drying, melted at 223- 225 C. with decomposition.

Example 2.3-(3-thiocarbamoyZ-Z-thioureido)phthalide 20.2 grams (0.15 mole) of dithiobiuret, 45.0 grams (0.30 mole) of phthalaldehydic acid and 200 milliliters of water were mixed and heated on the steam bath for 4 hours. During the course of the heating an amber colored oil slowly separated forming two layers. After completion of the heating, the aqueous layer was decanted from the mixture and cooled whereupon a solid precipitated. The latter was filtered from the mixture and dried to obtain a 3-(3-thiocarbamoyl-Z-thioureido)- phthalide product melting at 109-113 C.

The insecticidal properties of the phthalides may be illustrated by a representative operation wherein substantially complete mortality was observed when cockroaches (Periplaneta americana) were wetted with an aqueous composition containing 0.24 gram of 3-(3-thi0- agar media saturated with 3-(3-carbamoy1ureido)phthalide gave complete inhibition of growth when streaked with Salmonella typhosa and Staphylococcus aureus and incubated at 30 C. for 30 days.

The phthalaldehydic acid employed in this invention may be prepared by first photochlorinating o-xylene to obtain u,a,a,a',d-pentachloro-o-xylene by passing chlorine gas into o-xylene while illuminating with sun lamps. The resulting chlorinated o-xylene may be heated with an aqueous constant boiling hydrochloric acid and ferric chloride solution to obtain phthalaldehydic acid as more 15 fully disclosed in U. S. Patent 2,748,162.

4 We claim: 1. A phthalide having the formula wherein each X represents the same member selected from the group consisting of oxygen and sulfur.

2. 3-(S-carbamoylureido)phthalide. 3. 3-(3-thiocarbamoyl-Z-thioureido)phthalide.

No references cited. 

1. A PHTHALIDE HAVING THE FORMULA 